tbuckley/cabot-search huggingface dataset:
Abstract 13839: Knowledge, Attitude &amp; Practice of Health Care Workers Regarding Pediatric Early Warning System - A Cross Sectional Study in Karachi, Pakistan
Authors: Azwa Aziz, Qalab Abbas, Mehtab Jaffer, Noureen Sultan, Laila Ladak
Journal: Circulation (2021)

Introduction: The Pediatrics Early Warning Scoring (PEWS) system is a quantitative instrument that measures the severity of the clinical situation of children aged 1 month to 18 years. Hypothesis: To assess the knowledge, attitude, and practices among nurses and doctors regarding the Pediatric Early Warning Signs (PEWS) system, in a pediatric ward at a tertiary care hospital in Karachi, Pakistan. Methods: A cross-sectional study design was used to address the study question. The universal sampling technique was used to recruit a total of 142 eligible nurses and doctors to explore the knowledge and attitude regarding the PEWS system. Medical records of patients who had a Pediatric Rapid Response Team (PRRT) request raised was reviewed for practice assessment of PEWS. The relationship between the study participants’ demographic characteristics and their knowledge and attitude regarding PEWS was assessed through Chi-square for categorical variables and one-way ANOVA for continuous variables. Results: The findings of the study revealed that out of 142 study participants, 50% participants had a low level of knowledge yet positive attitude towards the PEWS system. Professional qualification and age of participants were significantly associated with knowledge regarding the PEWS system. Profession, professional qualification, current position of the study participants and specialized training on PEWS had a significant association with attitude regarding the PEWS system. Medical records of 30 patients were eligible for practice assessment which revealed that 56.7% of the PEWS observations were documented in patient records which were either incomplete or inappropriate. About 50% showed a poor level of practice regarding PEWS. Conclusions: Our study revealed a knowledge and practice gap among the nurses and doctors while utilizing the PEWS system. Despite having a low level of knowledge, the participants had a positive attitude towards PEWS to enhance their PEWS knowledge and practices. PEWS should be incorporated in the Pediatric Advanced Life Support (PALS) certification course. Moreover, simulation-based teaching strategies should be planned to improve practice and knowledge regarding the system.
Abstract 12111: Metformin Maintains Mitochondrial Integrity and Preserve Heart From Ischemia Reperfusion Injury Through Sestrin2-AMPK Signaling
Authors: Lauryn Bates, Julia Fedorova, Van Le, Yi Yang, Jiayuan Murphy, Kayla Davitt, Cole Logan, Di Ren, Ji Li
Journal: Circulation (2021)

Introduction: Metformin activates AMP-activated protein kinase (AMPK) to improve cardiac function during ischemia and reperfusion (I/R). We reported that Sestrin2 (Sesn2) is associated with AMPK and maintains oxidative phosphorylation (OXPHOS) under I/R stress. The role of age-related Sesn2-AMPK signaling in the beneficial actions of metformin on ischemic insults remains unknown. Hypothesis: Metformin maintains mitochondrial integrity and limits cardiac damage caused by ischemic insults through the Sesn2-AMPK signaling pathway. Methods: Young (3-6 months) and aged (22-24 months) C57BL/6J wild type mice, and 3 months of Sesn2 f/f and cardiomyocyte-specific Sesn2 knockout (cSesn2 -/- ) C57BL/6J mice were subjected to 45 minutes of ischemia followed by 2 mM metformin injection 5 minutes before 24-hour of reperfusion. Cardiac function and myocardial infarction were determined with echocardiography and 2,3,5-triphenyl tetrazolium chloride staining. Immunoblotting determines the mechanism of metformin in modulating Sesn2 to preserve mitochondrial OXPHOS components. The Seahorse XF Analyzer examined the mitochondrial respiratory functions. Results: Metformin administration can significantly improve cardiac function and reduce myocardial infarction size during I/R conditions in both young and aged wild-type C57BL/6J mice. Intriguingly, the beneficial effects of metformin administration on cardiac function and myocardial infarction were significantly blunted in the cSesn2 -/- versus Sesn2 f/f C57BL/6J mice. The immunoblotting showed metformin treatment augmented mitochondrial OXPHOS Complex II levels in young/aged wild type, and Sesn2 f/f but not cSesn2 -/- heart during I/R stress. Moreover, the mitochondrial respiration data displayed that metformin treatment improved the respiration rate of mitochondrial states 2 and 3μ in the isolated cardiomyocytes from Sens2 f/f but not from cSesn2 -/- mouse hearts under I/R stress conditions. Conclusions: Metformin can stabilize age-related Sesn2 levels in cardiomyocytes and improve cardiac function under I/R stress through maintaining mitochondrial integrity. Metformin is a potential therapeutic drug for ischemic heart disease in the elderly.
Abstract 14097: Pharmacometabolomic Profiling Of The General Population: Relation Of Active Metabolite Levels To Cardiovascular Risk Factor Control And Manifest Atherosclerosis
Authors: Madeleine Johansson, Nilanjana Ghosh, Carl Lejonberg, Tomasz Czuba, Maya Landenhed Smith, Tove Fall, Gunnar Engström, J. Gustav Smith
Journal: Circulation (2021)

Introduction: The use of medications in the general population has increased over time. Information on active metabolite concentrations for common drugs in the general population is limited. Recent advances in metabolomic technologies have made high-throughput profiling of many active metabolites in large epidemiological cohorts increasingly feasible. Aim: 1. Prospective assessment of the proportion of measurable active metabolite levels of major drugs in the general population using mass spectrometry. 2. Relation of cardiovascular (CV) drugs with inadequate risk factor control and CV disease. Methods: Assessment of CV risk factors by coronary CT angiography and carotid ultrasound imaging in a large prospective cohort of 6,251 individuals randomly selected from the general population in Malmö, Sweden (age 50-64 years). Untargeted metabolomic profiling of fasting plasma was performed by Metabolon, USA in a random subset of 3,986 subjects. Results: Intake of at least one prescribed drug was reported in 1840 subjects (46%). Combination drugs were reported in 249 subjects (6%). The most common drug classes reported were lipid-lowering (n=369, 9% of which most were statins), beta blockers (n=307, 8%), ARB (n=272, 7%), and ACE inhibitors (268, 7%), followed by levothyroxine, CCB, antidepressants, glucocorticoids, PPI, antidiabetic, bronchodilators and diuretics. For major CV drugs, detectable active metabolite levels ranged from 54% (atorvastatin and enalapril) to 96% (metoprolol and metformin). Non-detectable levels of lipid-lowering, antihypertensive, and antidiabetic drugs were associated with higher LDL, cholesterol, BP and glucose, although only antidiabetic drugs were significant (p&lt;0.05). Non-detectable levels of lipid-lowering and antihypertensive drugs were also non-significantly associated with increased coronary calcium and carotid plaque. Conclusion: Our study provides an overview of the distribution of common drugs with detectable levels in a contemporary Swedish population. Pharmacometabolomic profiling revealed that non-measurable levels of common CV drugs were associated with lower risk factor control and non-significant trends towards more atherosclerotic disease by imaging in a substantial number of subjects.
Abstract 12905: Left Atrial Appendage Arrhythmias in Patients With Epicardial or Endocardial Occlusive Devices
Authors: Katherine C Romanowicz, ALEXANDRU I COSTEA
Journal: Circulation (2021)

Background: The role of left atrial appendage (LAA) isolation in atrial fibrillation (AF) has been extensively studied. As this leads to loss of contractility, the risk for thromboembolism increases. Percutaneous occlusion of the left atrial appendage has been proven to prevent thromboembolisms, however, unlike epicardial ligation of the LAA, it does not provide electrical isolation. As such, the risk of recurrent atrial arrhythmias remains while an arrhythmia source originating around the occlusion device can be problematic. Objective: We present three patients with arrhythmias originating from the LAA after endocardial or epicardial occlusion. Utilizing ultra-high-density mapping a definition of arrhythmia circuit was delineated. Case Studies: Two patients with prior failed AF ablation prior to WATCHMAN TM implantation were referred for a second ablation. We created ultra-high-density maps processed the images with CARTO®3 Coherent mapping. CARTOSOUND® was used to delineate the WATCHMAN TM edges. Both patients were found to have arrhythmias originating from the LAA, proximal to the Watchman device. Delivery of radiofrequency ablation on the anterior aspect of the LAA stump in one patient and isolation of the LAA in the other patient terminated the arrhythmias. A third patient had a surgical closure of the LAA using an Atricure ® clamp as part of a conversion procedure. A recurrent arrhythmia was mapped inside the LAA, distal to the occluder. Ablation inside the LAA and through the Atricure® gap terminated the arrhythmia. Discussion: It is expected that the increasing prevalence of LAA occlusive devices will lead to an increase in atrial arrhythmias arising from the LAA post-occlusion. Conversely, electrical isolation of the LAA increases stroke risk. As the best staged approach for these patients remains unclear, a concomitant electrical isolation with ablation and LAA occlusion may be the optimal solution. Insufficient data and limiting healthcare economics prevent this approach from becoming a gold standard. Conclusion: Our cases confirm the LAA role in recurrent arrhythmias, highlight the difficult ablative management post LAA occlusion and support the use of high density mapping for a successful outcome.
Abstract 12142: Intravascular Ultrasound Guided Percutaneous Coronary Intervention Improves Acute Angiographic Results &amp; 1-year Clinical Outcomes for Patients With Chronic Total Occlusion
Authors: Jiachen BI, Kongto Hau, Bryan P Yan
Journal: Circulation (2021)

Introduction: Intravascular ultrasound (IVUS) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is not well established. This study aimed to evaluate IVUS-guided compared to angiography-only-guided CTO-PCI on acute angiographic result and 1-year clinical outcomes. Hypothesis: The application of IVUS in CTO-PCI could improve acute angiographic results and 1-year clinical outcomes for all-comers CTO patients. Methods: We analysed 528 consecutive patients undergoing CTO-PCI at a university affiliated hospital in Hong Kong from February 2009 to December 2016. Baseline characteristics, procedural characteristics, and 1-year clinical outcomes including cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and composite target lesion failure (TLF) were evaluated. The use of IVUS, and the choice of PCI devices including plain old balloon angioplasty (POBA), bare metal stent (BMS), and drug eluting stent (DES), were at the discretion of the operator. Propensity score matching (PSM) was performed to reduce treatment selection bias and potential confounding factors. Results: 275 patients underwent 288 angiography-only-guided and 253 patients underwent 268 IVUS-guided CTO-PCI. IVUS-guided CTO-PCI was associated with higher procedural success compared to angiography-only-guided CTO-PCI (77.5% vs. 55.3%, p&lt;0.01). DES were used more often in the IVUS-guided CTO-PCI group (85.3% vs. 65.6%, p&lt;0.01) while BMS were used less in IVUS-guided CTO-PCI group (9.3% vs. 26.1%). After PSM for successful CTO stented patients, angiography-IVUS guidance was associated with more post stent balloon dilatation (84.7% vs. 56.3%, p&lt;0.01), lower incidence of &gt;20% residual stenosis (2.2% vs. 10.8%, p&lt;0.01), longer total stent length (44.16±23.88mm vs. 33.52±18.90mm, p&lt;0.01), and larger final angiographic stented diameter (3.12±0.63mm vs. 2.94±0.48mm, p&lt;0.01). IVUS guided CTO-PCI was associated with lower 1-year TLF rates (3.0% vs. 10.0%, p=0.01). Conclusions: The use of IVUS was associated with higher success rates, more aggressive post-dilatation and better 1-year clinical outcomes compared to angiography-only guided CTO-PCI.
Meta-analysis of Randomized Controlled Trials
Authors: David Moher
Journal: JAMA (1995)

Evidence-based health care is becoming increasingly popular and, at least in some settings, is being used to assist in the creation of health care policy.<sup>1</sup>Meta-analyses are a key component of evidence-based health care. Such analyses pool individual randomized controlled trials (RCTs) together to arrive at an overall estimate of the effect of the intervention under consideration. Meta-analyses offer several potential advantages. They provide a systematic and explicit method for synthesizing evidence, a quantitative overall estimate (and confidence intervals) derived from the individual studies, and early evidence as to the effectiveness of treatments, thus reducing the need for continued study. They also can address questions in specific subgroups that individual studies may not have examined. There has been a striking increase in the number of published meta-analyses of RCTs. One of the first medical metaanalyses was published in<i>JAMA</i>in 1955.<sup>2</sup>By June 1992, the number of meta-analyses
ESGE news and upcoming events September 2022
Journal: Endoscopy (2022)

ESGE Research Grants support innovative, original research in gastroenterology. Potential contenders submit their research idea online. Our research committee reviews the applications and the top-rated proposals are selected. These applicants then take part in the ESGE Research Champions Den, at ESGE Days, where a jury of eminent researchers quiz the candidates, live. The best two or three are awarded research grants.
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: Prospective evaluation of the motorized spiral enteroscope for previous incomplete colonoscopyEndosc Int Open 2022; 10(08): E1112-E1117DOI: 10.1055/a-1869-2541 Comment on: Safety of teaching endoscopic ultrasound-guided gastroenterostomy (EUS-GE) can be improved with standardization of the techniqueEndosc Int Open 2022; 10(08): E1088-E1094DOI: 10.1055/a-1822-9864 Comment on: Thermal ablation of mucosal defect margins to prevent local recurrence of large colorectal polyps: a systematic review and meta-analysisEndosc Int Open 2022; 10(08): E1127-E1135DOI: 10.1055/a-1869-2446
Reply to Rana and Gupta
Authors: Radhika Chavan, Zaheer Nabi, Sundeep Lakhtakia, D. Nageshwar Reddy
Journal: Endoscopy (2022)

We thank Rana et al. for their interest and insightful comments on our recently published article [1]. In our study, metal stents were replaced with plastic stents after resolution of walled-off necrosis (WON). The clinical settings were different from those described in previous studies where index drainage was performed using plastic stents [2] [3]. We believe that this is a highly relevant scenario in the current era where large-caliber metal stents (LCMSs) are being increasingly utilized for the management of WON.
Commentary
Authors: Christian Gerges
Journal: Endoscopy (2022)

The authors present two cases with two different approaches to dealing with disconnected duct syndrome in patients with a collection. In both cases the collection was communicating with the disconnected main pancreatic duct (MPD) in the tail. In the first case, after initial drainage of the collection using a lumen-apposing metal stent and plastic stent, the plastic stent was left in place for indirect drainage of the MPD in the tail. In the second case, transgastric drainage of the MPD was established using a pigtail stent that was placed through the MPD into the fluid collection. Diagnosis and drainage of a disconnected duct is essential in these cases to prevent recurrent events of acute pancreatitis. Indirect drainage through the collection is effective and the plastic stents can usually be left in place for a very long time.
Thymosin β10 Inhibits Angiogenesis and Tumor Growth by Interfering with Ras Function
Authors: Seung-Hoon Lee, Myung Jin Son, Sun-Hee Oh, Seung-Bae Rho, Kyungsook Park, Yung-Jin Kim, Mi-Sun Park, Je-Ho Lee
Journal: Cancer Research (2005)

Abstract Thymosin β10 is a monomeric actin sequestering protein that regulates actin dynamics. Previously, we and others have shown that thymosin β10 acts as an actin-mediated tumor suppressor. In this study, we show that thymosin β10 is not only a cytoskeletal regulator, but that it also acts as a potent inhibitor of angiogenesis and tumor growth by its interaction with Ras. We found that overexpressed thymosin β10 significantly inhibited vascular endothelial growth factor–induced endothelial cell proliferation, migration, invasion, and tube formation in vitro. Vessel sprouting was also inhibited ex vivo. We further show that thymosin β10 directly interacted with Ras. This interaction resulted in inhibition of the Ras downstream mitogen-activated protein kinase/extracellular signal-regulated kinase kinase signaling pathway, leading to decreased vascular endothelial growth factor production. Thymosin β10 injected into a xenograft model of human ovarian cancer in nude mice markedly inhibited tumor growth and reduced tumor vascularity. In contrast, a related thymosin family member, thymosin β4, did not bind to Ras and showed positive effects on angiogenesis. These findings show that the inhibition of Ras signal transduction by thymosin β10 results in antiangiogenic and antitumor effects, suggesting that thymosin β10 may be valuable in anticancer therapy.
Long-term transmural plastic stenting after metal stent removal in disconnected pancreatic duct: is the debate over?
Authors: Surinder S. Rana, Rajesh Gupta
Journal: Endoscopy (2022)

See also: Impact of transmural plastic stent on recurrence of pancreatic fluid collection after metal stent removal in disconnected pancreatic duct: a randomized controlled trialEndoscopy 2022; 54(09): 861-868DOI: 10.1055/a-1747-3283
2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk
Authors: Donald M. Lloyd-Jones, Pamela B. Morris, Christie M. Ballantyne, Kim K. Birtcher, Ashleigh M. Covington, Sondra M. DePalma, Margo B. Minissian, Carl E. Orringer, Sidney C. Smith, Ashley Arana Waring, John T. Wilkins
Journal: Journal of the American College of Cardiology (2022)
Outcomes in Patients with Poor-Risk Cytogenetics with or without <i>TP53</i> Mutations Treated with Venetoclax and Azacitidine
Authors: Daniel A. Pollyea, Keith W. Pratz, Andrew H. Wei, Vinod Pullarkat, Brian A. Jonas, Christian Recher, Sunil Babu, Andre C. Schuh, Monique Dail, Yan Sun, Jalaja Potluri, Brenda Chyla, Courtney D. DiNardo
Journal: Clinical Cancer Research (2022)

To evaluate efficacy and safety of venetoclax + azacitidine in treatment-naïve patients with acute myeloid leukemia harboring poor-risk cytogenetics and TP53mut or TP53wt.We analyzed data from a phase III study (NCT02993523) comparing venetoclax (400 mg orally days 1-28) + azacitidine (75 mg/m2 days 1-7) or placebo + azacitidine, and from a phase Ib study (NCT02203773) of venetoclax + azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally.Patients (n = 127) with poor-risk cytogenetics receiving venetoclax + azacitidine (TP53wt = 50; TP53mut = 54) were compared with patients with poor-risk cytogenetics (n = 56) receiving azacitidine alone (TP53wt = 22; TP53mut = 18).For poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine versus azacitidine alone resulted in composite remission rates (CRc) of 70% versus 23%, median duration of remission (DoR) of 18.4 versus 8.5 months, and median overall survival (OS) of 23.4 versus 11.3 months, respectively. Outcomes with venetoclax + azacitidine were comparable with similarly treated patients with intermediate-risk cytogenetics and TP53wt.For poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine versus azacitidine alone resulted in CRc of 41% versus 17%, median DoR of 6.5 versus 6.7 months, and median OS of 5.2 versus 4.9 months, respectively.For poor-risk cytogenetics + TP53mut patients, predominant grade ≥3 adverse events (AE) for venetoclax + azacitidine versus azacitidine were febrile neutropenia (55%/39%), thrombocytopenia (28%/28%), neutropenia (26%/17%), anemia (13%/6%), and pneumonia (28%/33%). AEs were comparable between TP53mut and TP53wt patients.In poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine improved remission rates but not DoR or OS compared with azacitidine alone. However, in poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine resulted in higher remission rates and longer DoR and OS than azacitidine alone, with outcomes comparable with similarly treated patients with intermediate-risk cytogenetics. Toxicities were similar in TP53mut and TP53wt patients. See related commentary by Green and Zeidner, p. 5235.
High-Sensitivity Mutation Analysis of Cell-Free DNA for Disease Monitoring in Endometrial Cancer
Authors: Charles W. Ashley, Pier Selenica, Juber Patel, Michelle Wu, Josip Nincevic, Yulia Lakhman, Qin Zhou, Ronak H. Shah, Michael F. Berger, Arnaud Da Cruz Paula, David N. Brown, Antonio Marra, Alexia Iasonos, Amir Momeni-Boroujeni, Kaled M. Alektiar, Kara Long Roche, Oliver Zivanovic, Jennifer J. Mueller, Dmitriy Zamarin, Vance A. Broach, Yukio Sonoda, Mario M. Leitao, Claire F. Friedman, Elizabeth Jewell, Jorge S. Reis-Filho, Lora H. Ellenson, Carol Aghajanian, Nadeem R. Abu-Rustum, Karen Cadoo, Britta Weigelt
Journal: Clinical Cancer Research (2022)

Abstract Purpose: We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring. Experimental Design: Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods. Results: cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advanced-stage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and follow-up, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P &amp;lt; 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival. Conclusions: cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring. See related commentary by Grant et al., p. 305